42 articles - From Friday May 06 2022 to Friday May 13 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Blood Adv |
The ISHLT Chronic Lung Allograft Dysfunction Consensus Criteria is Applicable to Pulmonary Chronic Graft-versus-Host Disease. The NIH- subjects showed increased risk of death compared to those without PcGvHD (HR = 1.88, 95%CI = 1.20-2.95, p = 0.006) that was similar to NIH+ subjects (p = 0.678). Our study demonstrated the potential of the Adapted Criteria in identifying high risk PcGvHD patients that have been missed by the NIH Criteria. The Adapted Criteria could become a valuable tool to better phenotype and study lung disease in cGvHD. |
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Ann Oncol |
Deciphering radiological stable disease to immune checkpoint inhibitors. RECIST-defined SD to immunotherapy is common, heterogenous, and may largely reflect tumor growth rate rather than ICI response. In patients with NSCLC and SD to ICIs, PFS>6 months and no tumor growth may be considered "SD responders." This definition may improve the efficiency of and insight derivable from clinical and translational research. |
Prognostic stratification of HPV associated oropharyngeal cancer based on CD103+ immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomised trials. CD103 + ITIC expression separates CETUX/RT treated low risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials. |
Treatment Efficacy Score - continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials. In the validation set, TES identified arms with higher pCR rate but was more accurate to identify regimens as less effective if treatment did not reduce the frequency of high RCB values, even if pCR rate improved. The correlation between TES and survival was higher than the correlation between pCR rate difference and survival. TES quantifies the difference between the entire distribution of pathologic responses observed in trial arms and could serve as a better early surrogate to predict trial arm level survival differences than pCR rate difference alone. |
| Blood |
Combination therapies to inhibit LCK tyrosine kinase and mTOR signaling in T-cell Acute Lymphoblastic Leukemia. Mechanistically, dasatinib inhibited phosphorylation and activation of the lymphocyte-specific protein tyrosine kinase (LCK) to blunt the T-cell receptor (TCR) signaling pathway and when complexed with mTORC1 inhibition, induced potent T-ALL cell killing through reducing MCL-1 protein expression. In total, our work uncovered unexpected roles for the LCK kinase and its regulation of downstream TCR signaling in suppressing apoptosis and driving continued leukemia growth. Analysis of a wide array of primary human T-ALLs and PDXs grown in mice suggest that combination of temsirolimus and dasatinib treatment will be efficacious for a large fraction of human T-ALLs. |
COVID-19 in patients with hematologic malignancy. These therapies should be offered to patients at high risk for severe COVID-19 and vaccine non-responder. Importantly, as the virus evolves, some therapies may lose their clinical efficacy against new variants. Therefore, the ongoing pandemic will remain a major challenge for patients with hematologic malignancy and their caregivers who need to constantly monitor the scientific progress in this area. |
Functional, structural and molecular characterizations of leukemogenic driver MEF2D-HNRNPUL1 fusion. The C-terminal moiety (HNRNPUL1 part) of MH was proven to contribute to the fusion protein's trans-regulatory activity, co-factors recruitment and homodimerization. Furthermore, targeting MH-driven transactivation of HDAC family using HDAC inhibitor Panobinostat improved the overall survival of MH/NRASG12D BCP-ALL mice in combination with chemotherapy. Altogether, these results not only highlight MH as an important driver in leukemogenesis, but also provoke targeted intervention against BCP-ALL with MEF2D fusions. |
How I treat high-risk acute myeloid leukemia using pre-emptive adoptive cellular immunotherapy. To prevent impending relapse, a number of groups have explored administering DLI pre-emptively upon detection of measurable residual disease (MRD) or mixed chimerism (MC). Evidence for the effectiveness of this strategy, while encouraging, comes from only a few, mostly single-center retrospective, non-randomized studies. This article seeks to i) discuss the available evidence supporting this approach while highlighting some of the inherent challenges of MRD-triggered treatment decisions post-transplant, ii) portray other forms of post-remission cellular therapies, including the role of next-generation target-specific immunotherapies and iii) provide a practical framework to support clinicians in their decision-making process when considering pre-emptive cellular therapy for this difficult-to-treat patient population. |
Impact of Etoposide and ASCT on Survival Among Patients <65 years With Stage II-IV PTCL; a Population-Based Cohort Study. When adjusted for subtype, IPI-score, and ASCT, the risk of mortality was similar between the two groups, except for ALK+ ALCL patients for whom risk of mortality was 6.3 times higher when treated with CHOP as compared to CHOEP. Patients consolidated with ASCT demonstrated a superior 5-year OS of 81% as compared to 39% for patients not receiving an ASCT (p<0·01), regardless of whether a complete remission was achieved. In patients <65 years with advanced stage ALK- ALCL, AITL and PTCL, the use of ASCT consolidation, but not the addition of etoposide, was associated with improved OS. |
Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms. We demonstrated experimentally that lenalidomide treatment provides a selective advantage to Trp53-mutant hematopoietic stem and progenitor cells (HSPCs) in vitro and in vivo, the effect of which was specific to Trp53-mutant HSPCs and was not observed in HSPCs with other CH mutations. Due to differences in CK1a degradation, pomalidomide treatment did not provide an equivalent level of selective advantage to Trp53-mutant HSPCs providing a biological rationale for its use in patients at high risk for t-MN. These findings highlight the role of lenalidomide treatment in promoting TP53-mutated t-MNs and offer a potential alternative strategy to mitigate the risk of t-MN development. |
Risk assessment with low pass whole genome sequencing of cell free DNA before CD19 CAR T-cells for large B-cell lymphoma. In multivariable selection, high focal CNA score (FCS) denoting genomic instability was the most significant pretreatment variable associated with inferior 3-month complete response rates (28% versus 56%, p=0.0029), progression free survival (PFS) (p=0.0007, hazard ratio 2.11) and overall survival (OS) (p=0.0026, hazard ratio 2.10). We identified 34 unique focal CNAs in 108 (89%) patients; of these, deletion 10q23.3 leading to loss of FAS death receptor was the most prognostic for poor outcomes, leading to inferior PFS (p 1 extranodal sites), we built a simple risk model that could reliably risk stratify patients. Thus, lpWGS of cfDNA is a minimally invasive assay that could rapidly identify high-risk patients and may guide patient selection for and targeted therapies to evaluate in future clinical trials. |
| Blood Adv |
Code Status Transitions in Patients with High-Risk Acute Myeloid Leukemia. Younger age (B=0.04, P=0.002) and informative conversations (B=-2.79, P<0.001) were associated with shorter time from last transition to death. Over two-thirds of patients were "presumed full code" at diagnosis of high-risk AML, and most experienced code status transitions focused on futility of continuing life-sustaining therapies near EOL. These results suggest that goals-of-care discussions occur late in the illness course for patients with AML and warrant interventions to increase earlier discussions regarding EOL preferences. |
Complement Gene Variant Effect on Relapse of Complement-Mediated Thrombotic Microangiopathy after Eculizumab Cessation. Presence of a renal allograft (p=0.009); decreasing age (p=0.029); and detection of variants in CFH (p<0.001), MCP/CD46 (p<0.001) or C3 (p<0.001) were al independently associated with relapse after eculizumab discontinuation. Eculizumab discontinuation is appropriate in specific patients with CM-TMA. Caution should be exerted when attempting such a strategy in patients with high risk of recurrence, including a subgroup of patients with MCP/CD46 variants. |
Enhanced VWF clearance in Low VWF pathogenesis - limitations of VWFpp/VWF:Ag ratio and clinical significance. Importantly from a clinical perspective, this enhanced VWF clearance was seen following desmopressin infusion, but did not affect the steady-state VWFpp/VWF:Ag ratio in most cases. This discrepancy between VWFpp/VWF:Ag ratio and desmopressin fall-off rates in patients with mild quantitative VWD may reflect alteration in VWFpp clearance kinetics. Finally, our data further demonstrate that bleeding scores are significantly lower in Low VWF patients with enhanced VWF clearance compared to those in whom reduced VWF biosynthesis represents the principle pathogenic mechanism. |
Genome-wide association study of platelet factor 4/heparin antibodies in heparin-induced thrombocytopenia. The top variant in both cohorts was rs1555175145 (discovery ß=-0.112[0.018], p=2.50x10-5; replication ß=-0.104[0.051], p=0.041). In gene set enrichment analysis (GSEA), three gene sets reached false discovery rate-adjusted significance (q<0.05) in both discovery and replication cohorts: "Leukocyte Transendothelial Migration," "Innate Immune Response," and "Lyase Activity." Our results indicate that genomic variation is not significantly associated with anti-PF4/heparin antibody levels. Given our power to identify variants with moderate frequencies and effect sizes, this evidence suggests genetic variation is not a primary driver of variable antibody response in heparin-treated patients with European ancestry. |
High-sensitivity next-generation sequencing MRD assessment in ALL identifies patients at very low risk of relapse. NGS MRD negativity at CR was associated with significantly decreased risk of relapse compared with MRD positivity (5-year CIR: 0% versus 45%, respectively, P=0.04). Among patients who were MRD negative by MFC, detection of low levels of MRD by NGS identified patients who still had a significant risk of relapse (5-year CIR: 39%). Early assessment of MRD using a highly sensitive NGS assay adds clinically relevant prognostic information to standard MFC-based approaches and can identify patients with ALL undergoing frontline therapy who have a very low risk of relapse and excellent long-term survival. |
Impaired exercise capacity in post-COVID syndrome: the role of VWF-ADAMTS13 axis. 20% (56/276) had impaired exercise capacity, of which 55% (31/56) had a raised VWF(Ag):ADAMTS13 ratio =1.5 (p<0.0001). FVIII and VWF(Ag) were elevated in 26% and 18% respectively and support a hypercoagulable state in some patients with PCS. These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and highlight a potential role for antithrombotic therapy in the management of these patients. |
Incidence of Acquired Pure Red Cell Aplasia: A Nationwide Epidemiologic Analysis With 2 Registry Databases in Japan. The incidence of PRCA was approximately 20% that of aplastic anemia during the same period. Approximately 0.98 patients per million per year (95% CI: 0.89-1.07) required hospitalization for the treatment of PRCA. These results are expected to contribute to the discussion of resource allocation for PRCA in the aging population in many countries, including Japan. |
Relationship of iothalamate clearance and NRM in patients receiving fludarabine and melphalan reduced-intensity conditioning. In the 109 included patients, mGFR < 65 ml/min/1.73m2 predicted a significantly higher rate of overall NRM (HR 2.13, 95% CI, 1.03-4.35, P = 0.04) and 1-year incidence of infection (HR 2.63, 95% CI, 1.54-4.55, P < 0.001) in addition to a significantly lower 2-year survival (P = 0.019). Kidney function estimated via eGFR and eCrCl did not correlate with post-transplant outcomes. These results suggest that mGFR is a promising approach for assessing clearance in allogeneic HSCT patients and may be preferred to standard creatinine-based eGFR strategies. |
SAKK 35/15: a phase 1 trial of obinutuzumab in combination with venetoclax in patients with previously untreated follicular lymphoma. One-year progression-free survival was 77.8% (95% CI, 54.6-90.1%) and 79% (95% CI, 47.9-92.7%) for CT and PET/CT evaluable patients, respectively, while progression-free survival at 30 months was 73.2% (95% CI, 49.8%, 87.0%) as assessed by CT and 79.0% (95% CI, 47.9%, 92.7%) by PET/CT. Despite the activity observed our results do not support further development of the combination in this patient population. This trial is registered at as NCT02877550. |
The bleeding phenotype in people with non-severe hemophilia. Baseline FVIII/IX was inversely associated with the joint bleeding rate (p <0.001). Low bleeding rates were observed in people with non-severe hemophilia. However, half of al adolescents and adults had experienced a joint bleed. |
The landscape of immunoglobulin heavy chain gene repertoire and its clinical relevance in LPL/WM. IGHV3-23 and IGHV3-74 segments were more frequently detected in mutated MYD88 LPL/WM patients (P=0.050), while IGHV3-7 presented more frequently in MYD88 wild-type patients (P=0.042). Patients with IGHV4, especially IGHV4-34, had higher levels of lactate dehydrogenase, and IGHV4 was a predictive marker of shorter progression-free survival. These results showed for the first time that the IGHV repertoire has clinical relevance in LPL/WM. |
| Haematologica |
COVID-19 in adult acute myeloid leukemia patients: a long-term followup study from the European Hematology Association survey (EPICOVIDEHA). After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with an improved survival when AML treatment could be delayed (80%; p. |
Focal structural variants revealed by whole genome sequencing disrupt the histone demethylase KDM4C in B cell lymphomas. By integrating RNAseq and genome sequencing data we predict KDM4C structural variants to result in loss-of-function. By functional reconstitution studies in cell lines, we provide evidence that KDM4C can act as tumor suppressor. Thus, we show that identification of structural variants in whole genome sequencing data adds to the comprehensive description of the mutational landscape of lymphomas and, moreover, establish KDM4C as putative tumor suppressive gene recurrently altered in subsets of B-cell derived lymphomas. |
| J Hematol Oncol |
A novel tRNA-derived fragment AS-tDR-007333 promotes the malignancy of NSCLC via the HSPB1/MED29 and ELK4/MED29 axes. Our study identifies a new oncogenic tRF and uncovers a novel mechanism that AS-tDR-007333 promotes NSCLC malignancy through the HSPB1-MED29 and ELK4-MED29 axes. AS-tDR-007333 is a potential diagnostic or prognostic marker and therapeutic target for NSCLC. |
LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma. This study found that LncRNA-PACERR functions as key regulator of TAMs in PDAC microenvironment and revealed the novel mechanisms in cytoplasm and in nucleus. |
SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders. Our study highlights the benefit of developing an antibody response in these highly immunosuppressed patients. Level of antibody titers at 3 to 6 weeks after 2-dose vaccination links with protection against both breakthrough infection and severe disease for non-Omicron SARS-CoV-2 variants. |
| Lancet Haematol |
Venetoclax plus 3 These findings are an important contribution to the field, showing a safe strategy to incorporate venetoclax into the most common induction regimen used to treat newly diagnosed acute myeloid leukaemia internationally. Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang, National Natural Science Foundation of China, Key Research and Development Program of Zhejiang. For the Chinese translation of the abstract see Supplementary Materials section. |
| Leukemia |
Ceramide synthase 6 impacts T-cell allogeneic response and graft-versus-host disease through regulating N-RAS/ERK pathway. At the cellular level, blockade of CerS6 restrained donor T cells from migrating into GVHD target organs and preferentially reduced activation of donor CD4 T cells. At the molecular level, CerS6 was required for optimal TCR signaling, CD3/PKC |
The scaffold protein NEDD9 is necessary for leukemia-cell migration and disease progression in a mouse model of chronic lymphocytic leukemia. Additionally, CLL lymph nodes frequently expressed high NEDD9 levels, with a subset of patients showing NEDD9 expression enriched in the CLL proliferation centers. Blocking activity of prominent NEDD9 effectors, including AURKA and HDAC6, effectively reduced CLL cell migration and chemotaxis. Collectively, our study provides evidence for a functional role of NEDD9 in CLL pathogenesis that involves intrinsic defects in adhesion, migration and homing. |
| Thromb Haemost |
Hemorrhages in polycythemia vera and essential thrombocythemia: epidemiology, description, and risk factors, learnings from a large cohort. The morbidity and mortality of bleedings in MPN should not be underestimated, and some patients could beneficiate from cytoreduction in order to reducing bleeding risk. Iatrogenic bleedings represent a substantial proportion of bleeding and could be better prevented. |
Platelet Activation via Glycoprotein VI Initiates Thrombin Generation: A Potential Role for Platelet-Derived Factor IX? In a purified system composed of FX and FVIII, we observed that absence of FIX was compensated by GPVI-activated platelets, which could be inhibited by an anti-FIX antibody, suggesting FIXa activity from activated platelets. Furthermore, with the addition of FVIII in FIX-deficient plasma, TG induced by GPVI-activated platelets was restored, and was inhibited by the anti-FIX antibody. In conclusion, GPVI-activated platelets initiate TG, probably via platelet-derived FIXa activity. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| J Hematol Oncol |
The dual role of autophagy in acute myeloid leukemia. e., the inhibitors and activators, are described as potential therapeutics for AML. Finally, we describe the translation of autophagy-modulating therapeutics into clinical practice. Autophagy in AML is a double-edged sword, necessitating a deeper understanding of how autophagy influences dual functions in AML tumorigenesis and anti-leukemic responses. |
| Lancet Haematol |
An integrated approach to cardioprotection in lymphomas. In this Review, we summarise the mechanisms of treatment-related cardiac injury, available clinical data, and protocols for optimising cardioprotection in lymphomas. We discuss ongoing research strategies to advance our knowledge of the molecular basis of drug-induced and radiation-induced toxicity. Additionally, we emphasise the potential for personalised follow-up and early detection, including the role of biomarkers and novel diagnostic tests, highlighting the role of the cardio-oncology team. |
Letters to the editors and authors’ replies
| Ann Oncol |
| J Hematol Oncol |
A novel role of lysophosphatidic acid (LPA) in human myeloma resistance to proteasome inhibitors. Importantly, inhibiting LPAR2 activity or knocking out LPAR2 in MM cells significantly enhanced MM sensitivity to PI-induced apoptosis in vitro and in vivo. Interestingly, primary MM cells from LPA-high patients were more resistant to PI-induced apoptosis than MM cells from LPA-low patients. Thus, our study indicates that LPA-LPAR2-mediated signaling pathways play an important role in MM sensitivity to PIs and targeting LPA or LPAR2 may potentially be used to (re)sensitize patients to PI-based therapy. |
Pevonedistat in East Asian patients with acute myeloid leukemia or myelodysplastic syndromes: a phase 1/1b study to evaluate safety, pharmacokinetics and activity as a single agent and in combination with azacitidine. This study showed that the pharmacokinetic and safety profiles of pevonedistat plus azacitidine in East Asian patients were similar to those observed in Western patients as previously reported. The recommended Phase 2/3 dose (RP2/3D) of pevonedistat was determined to be 20 mg/m 2 for co-administration with azacitidine 75 mg/m 2 in Phase 2/3 studies, which was identical to the RP2/3D established in Western patients.: clinicaltrials. gov: NCT02782468 25 May 2016. |
all remaining publications eg case reports, images of the month, etc…
| Blood |
| Blood Adv |
| Lancet Haematol |